Caspase inhibitors improve survival in sepsis: a critical role of the lymphocyte
Sepsis induces lymphocyte apoptosis and prevention of lymphocyte death may improve the chances of surviving this disorder. We compared the efficacy of a selective caspase-3 inhibitor to a polycaspase inhibitor and to caspase-3 −/− mice. Both inhibitors prevented lymphocyte apoptosis and improved sur...
Gespeichert in:
| Veröffentlicht in: | Nature immunology 2000-12, Vol.1 (6), p.496-501 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 501 |
|---|---|
| container_issue | 6 |
| container_start_page | 496 |
| container_title | Nature immunology |
| container_volume | 1 |
| creator | Hotchkiss, R. S. Chang, K. C. Swanson, P. E. Tinsley, K. W. Hui, J. J. Klender, P. Xanthoudakis, S. Roy, S. Black, C. Grimm, E. Aspiotis, R. Han, Y. Nicholson, D. W. Karl, I. E. |
| description | Sepsis induces lymphocyte apoptosis and prevention of lymphocyte death may improve the chances of surviving this disorder. We compared the efficacy of a selective caspase-3 inhibitor to a polycaspase inhibitor and to caspase-3
−/−
mice. Both inhibitors prevented lymphocyte apoptosis and improved survival. Caspase-3
−/−
mice shared a decreased, but not total, block of apoptosis. The polycaspase inhibitor caused a very substantial decrease in bacteremia. Caspase inhibitors did not benefit RAG-1
−/−
mice, which had a >tenfold increase in bacteremia compared to controls. Adoptive transfer of T cells that overexpressed the anti-apoptotic protein Bcl-2 increased survival. T cells stimulated with anti-CD3 and anti-CD28 produced increased interleukin 2 and interferon γ by 6 h. Thus, caspase inhibitors enhance immunity by preventing lymphocyte apoptosis and lymphocytes act rapidly, within 24 h, to control infection. |
| doi_str_mv | 10.1038/82741 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_72590301</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A188805796</galeid><sourcerecordid>A188805796</sourcerecordid><originalsourceid>FETCH-LOGICAL-c435t-553be4ce7755efb4bdec8da060d475ec3b0588e23334b82525d6f55e94ee64ae3</originalsourceid><addsrcrecordid>eNqFkd9rFDEQx4Motrb9FyQIFvpwNT83Wd_KYbVQsGh9Dtns7F3K7mZNsof335t6h8f5IvMww8xnhvnyReiCkmtKuP6gmRL0BTqlktULVtPq5d-a6BP0JqUnQqhQlXiNTiilhGpFT9HD0qbJJsB-XPvG5xAT9sMUwwZwmuPGb2xfZjjBlHz6iC120WfvSjeGHnDocF4D7rfDtA5um-Ecvepsn-Bin8_Qj9tPj8svi_uvn--WN_cLJ7jMCyl5A8KBUlJC14imBadbSyrSCiXB8YZIrYFxzkWjmWSyrbqC1gKgEhb4Gbrc3S2__pwhZTP45KDv7QhhTkYxWRNO6H9BqpQWFdcFfPcP-BTmOBYRhjGmKCdVXaDrHbSyPRg_diFH60q0MHgXRuh86d9QrTWRqq7KwtXRQmEy_MorO6dk7r5_O2bf71gXQ0oROjNFP9i4NZSYZ5fNH5cL93b_6dwM0B6ova0HzamMxhXEg5TjS78B8mOrmA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>222713069</pqid></control><display><type>article</type><title>Caspase inhibitors improve survival in sepsis: a critical role of the lymphocyte</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><source>Nature Journals Online</source><creator>Hotchkiss, R. S. ; Chang, K. C. ; Swanson, P. E. ; Tinsley, K. W. ; Hui, J. J. ; Klender, P. ; Xanthoudakis, S. ; Roy, S. ; Black, C. ; Grimm, E. ; Aspiotis, R. ; Han, Y. ; Nicholson, D. W. ; Karl, I. E.</creator><creatorcontrib>Hotchkiss, R. S. ; Chang, K. C. ; Swanson, P. E. ; Tinsley, K. W. ; Hui, J. J. ; Klender, P. ; Xanthoudakis, S. ; Roy, S. ; Black, C. ; Grimm, E. ; Aspiotis, R. ; Han, Y. ; Nicholson, D. W. ; Karl, I. E.</creatorcontrib><description>Sepsis induces lymphocyte apoptosis and prevention of lymphocyte death may improve the chances of surviving this disorder. We compared the efficacy of a selective caspase-3 inhibitor to a polycaspase inhibitor and to caspase-3
−/−
mice. Both inhibitors prevented lymphocyte apoptosis and improved survival. Caspase-3
−/−
mice shared a decreased, but not total, block of apoptosis. The polycaspase inhibitor caused a very substantial decrease in bacteremia. Caspase inhibitors did not benefit RAG-1
−/−
mice, which had a >tenfold increase in bacteremia compared to controls. Adoptive transfer of T cells that overexpressed the anti-apoptotic protein Bcl-2 increased survival. T cells stimulated with anti-CD3 and anti-CD28 produced increased interleukin 2 and interferon γ by 6 h. Thus, caspase inhibitors enhance immunity by preventing lymphocyte apoptosis and lymphocytes act rapidly, within 24 h, to control infection.</description><identifier>ISSN: 1529-2908</identifier><identifier>EISSN: 1529-2916</identifier><identifier>DOI: 10.1038/82741</identifier><identifier>PMID: 11101871</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Adoptive Transfer ; Animals ; Apoptosis - drug effects ; Bacteremia - drug therapy ; Bacteremia - microbiology ; Bacteremia - pathology ; Biomedical and Life Sciences ; Biomedicine ; Caspase 3 ; Caspase Inhibitors ; Caspases - genetics ; Colony Count, Microbial ; Cysteine Proteinase Inhibitors - pharmacology ; Female ; Homeodomain Proteins - genetics ; Homeodomain Proteins - metabolism ; Humans ; Immunology ; In Vitro Techniques ; Infectious Diseases ; Inhibitors ; Interferon-gamma - biosynthesis ; Interleukin-2 - biosynthesis ; Lymphocytes ; Lymphocytes - drug effects ; Lymphocytes - pathology ; Mice ; Mice, Knockout ; Prevention ; Sepsis - drug therapy ; Sepsis - pathology ; Survival</subject><ispartof>Nature immunology, 2000-12, Vol.1 (6), p.496-501</ispartof><rights>Nature America Inc. 2000</rights><rights>COPYRIGHT 2000 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Dec 2000</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c435t-553be4ce7755efb4bdec8da060d475ec3b0588e23334b82525d6f55e94ee64ae3</citedby><cites>FETCH-LOGICAL-c435t-553be4ce7755efb4bdec8da060d475ec3b0588e23334b82525d6f55e94ee64ae3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/82741$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/82741$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11101871$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hotchkiss, R. S.</creatorcontrib><creatorcontrib>Chang, K. C.</creatorcontrib><creatorcontrib>Swanson, P. E.</creatorcontrib><creatorcontrib>Tinsley, K. W.</creatorcontrib><creatorcontrib>Hui, J. J.</creatorcontrib><creatorcontrib>Klender, P.</creatorcontrib><creatorcontrib>Xanthoudakis, S.</creatorcontrib><creatorcontrib>Roy, S.</creatorcontrib><creatorcontrib>Black, C.</creatorcontrib><creatorcontrib>Grimm, E.</creatorcontrib><creatorcontrib>Aspiotis, R.</creatorcontrib><creatorcontrib>Han, Y.</creatorcontrib><creatorcontrib>Nicholson, D. W.</creatorcontrib><creatorcontrib>Karl, I. E.</creatorcontrib><title>Caspase inhibitors improve survival in sepsis: a critical role of the lymphocyte</title><title>Nature immunology</title><addtitle>Nat Immunol</addtitle><addtitle>Nat Immunol</addtitle><description>Sepsis induces lymphocyte apoptosis and prevention of lymphocyte death may improve the chances of surviving this disorder. We compared the efficacy of a selective caspase-3 inhibitor to a polycaspase inhibitor and to caspase-3
−/−
mice. Both inhibitors prevented lymphocyte apoptosis and improved survival. Caspase-3
−/−
mice shared a decreased, but not total, block of apoptosis. The polycaspase inhibitor caused a very substantial decrease in bacteremia. Caspase inhibitors did not benefit RAG-1
−/−
mice, which had a >tenfold increase in bacteremia compared to controls. Adoptive transfer of T cells that overexpressed the anti-apoptotic protein Bcl-2 increased survival. T cells stimulated with anti-CD3 and anti-CD28 produced increased interleukin 2 and interferon γ by 6 h. Thus, caspase inhibitors enhance immunity by preventing lymphocyte apoptosis and lymphocytes act rapidly, within 24 h, to control infection.</description><subject>Adoptive Transfer</subject><subject>Animals</subject><subject>Apoptosis - drug effects</subject><subject>Bacteremia - drug therapy</subject><subject>Bacteremia - microbiology</subject><subject>Bacteremia - pathology</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Caspase 3</subject><subject>Caspase Inhibitors</subject><subject>Caspases - genetics</subject><subject>Colony Count, Microbial</subject><subject>Cysteine Proteinase Inhibitors - pharmacology</subject><subject>Female</subject><subject>Homeodomain Proteins - genetics</subject><subject>Homeodomain Proteins - metabolism</subject><subject>Humans</subject><subject>Immunology</subject><subject>In Vitro Techniques</subject><subject>Infectious Diseases</subject><subject>Inhibitors</subject><subject>Interferon-gamma - biosynthesis</subject><subject>Interleukin-2 - biosynthesis</subject><subject>Lymphocytes</subject><subject>Lymphocytes - drug effects</subject><subject>Lymphocytes - pathology</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Prevention</subject><subject>Sepsis - drug therapy</subject><subject>Sepsis - pathology</subject><subject>Survival</subject><issn>1529-2908</issn><issn>1529-2916</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkd9rFDEQx4Motrb9FyQIFvpwNT83Wd_KYbVQsGh9Dtns7F3K7mZNsof335t6h8f5IvMww8xnhvnyReiCkmtKuP6gmRL0BTqlktULVtPq5d-a6BP0JqUnQqhQlXiNTiilhGpFT9HD0qbJJsB-XPvG5xAT9sMUwwZwmuPGb2xfZjjBlHz6iC120WfvSjeGHnDocF4D7rfDtA5um-Ecvepsn-Bin8_Qj9tPj8svi_uvn--WN_cLJ7jMCyl5A8KBUlJC14imBadbSyrSCiXB8YZIrYFxzkWjmWSyrbqC1gKgEhb4Gbrc3S2__pwhZTP45KDv7QhhTkYxWRNO6H9BqpQWFdcFfPcP-BTmOBYRhjGmKCdVXaDrHbSyPRg_diFH60q0MHgXRuh86d9QrTWRqq7KwtXRQmEy_MorO6dk7r5_O2bf71gXQ0oROjNFP9i4NZSYZ5fNH5cL93b_6dwM0B6ova0HzamMxhXEg5TjS78B8mOrmA</recordid><startdate>20001201</startdate><enddate>20001201</enddate><creator>Hotchkiss, R. S.</creator><creator>Chang, K. C.</creator><creator>Swanson, P. E.</creator><creator>Tinsley, K. W.</creator><creator>Hui, J. J.</creator><creator>Klender, P.</creator><creator>Xanthoudakis, S.</creator><creator>Roy, S.</creator><creator>Black, C.</creator><creator>Grimm, E.</creator><creator>Aspiotis, R.</creator><creator>Han, Y.</creator><creator>Nicholson, D. W.</creator><creator>Karl, I. E.</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ISR</scope><scope>3V.</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20001201</creationdate><title>Caspase inhibitors improve survival in sepsis: a critical role of the lymphocyte</title><author>Hotchkiss, R. S. ; Chang, K. C. ; Swanson, P. E. ; Tinsley, K. W. ; Hui, J. J. ; Klender, P. ; Xanthoudakis, S. ; Roy, S. ; Black, C. ; Grimm, E. ; Aspiotis, R. ; Han, Y. ; Nicholson, D. W. ; Karl, I. E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c435t-553be4ce7755efb4bdec8da060d475ec3b0588e23334b82525d6f55e94ee64ae3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Adoptive Transfer</topic><topic>Animals</topic><topic>Apoptosis - drug effects</topic><topic>Bacteremia - drug therapy</topic><topic>Bacteremia - microbiology</topic><topic>Bacteremia - pathology</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Caspase 3</topic><topic>Caspase Inhibitors</topic><topic>Caspases - genetics</topic><topic>Colony Count, Microbial</topic><topic>Cysteine Proteinase Inhibitors - pharmacology</topic><topic>Female</topic><topic>Homeodomain Proteins - genetics</topic><topic>Homeodomain Proteins - metabolism</topic><topic>Humans</topic><topic>Immunology</topic><topic>In Vitro Techniques</topic><topic>Infectious Diseases</topic><topic>Inhibitors</topic><topic>Interferon-gamma - biosynthesis</topic><topic>Interleukin-2 - biosynthesis</topic><topic>Lymphocytes</topic><topic>Lymphocytes - drug effects</topic><topic>Lymphocytes - pathology</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Prevention</topic><topic>Sepsis - drug therapy</topic><topic>Sepsis - pathology</topic><topic>Survival</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hotchkiss, R. S.</creatorcontrib><creatorcontrib>Chang, K. C.</creatorcontrib><creatorcontrib>Swanson, P. E.</creatorcontrib><creatorcontrib>Tinsley, K. W.</creatorcontrib><creatorcontrib>Hui, J. J.</creatorcontrib><creatorcontrib>Klender, P.</creatorcontrib><creatorcontrib>Xanthoudakis, S.</creatorcontrib><creatorcontrib>Roy, S.</creatorcontrib><creatorcontrib>Black, C.</creatorcontrib><creatorcontrib>Grimm, E.</creatorcontrib><creatorcontrib>Aspiotis, R.</creatorcontrib><creatorcontrib>Han, Y.</creatorcontrib><creatorcontrib>Nicholson, D. W.</creatorcontrib><creatorcontrib>Karl, I. E.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Nature immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hotchkiss, R. S.</au><au>Chang, K. C.</au><au>Swanson, P. E.</au><au>Tinsley, K. W.</au><au>Hui, J. J.</au><au>Klender, P.</au><au>Xanthoudakis, S.</au><au>Roy, S.</au><au>Black, C.</au><au>Grimm, E.</au><au>Aspiotis, R.</au><au>Han, Y.</au><au>Nicholson, D. W.</au><au>Karl, I. E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Caspase inhibitors improve survival in sepsis: a critical role of the lymphocyte</atitle><jtitle>Nature immunology</jtitle><stitle>Nat Immunol</stitle><addtitle>Nat Immunol</addtitle><date>2000-12-01</date><risdate>2000</risdate><volume>1</volume><issue>6</issue><spage>496</spage><epage>501</epage><pages>496-501</pages><issn>1529-2908</issn><eissn>1529-2916</eissn><abstract>Sepsis induces lymphocyte apoptosis and prevention of lymphocyte death may improve the chances of surviving this disorder. We compared the efficacy of a selective caspase-3 inhibitor to a polycaspase inhibitor and to caspase-3
−/−
mice. Both inhibitors prevented lymphocyte apoptosis and improved survival. Caspase-3
−/−
mice shared a decreased, but not total, block of apoptosis. The polycaspase inhibitor caused a very substantial decrease in bacteremia. Caspase inhibitors did not benefit RAG-1
−/−
mice, which had a >tenfold increase in bacteremia compared to controls. Adoptive transfer of T cells that overexpressed the anti-apoptotic protein Bcl-2 increased survival. T cells stimulated with anti-CD3 and anti-CD28 produced increased interleukin 2 and interferon γ by 6 h. Thus, caspase inhibitors enhance immunity by preventing lymphocyte apoptosis and lymphocytes act rapidly, within 24 h, to control infection.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>11101871</pmid><doi>10.1038/82741</doi><tpages>6</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1529-2908 |
| ispartof | Nature immunology, 2000-12, Vol.1 (6), p.496-501 |
| issn | 1529-2908 1529-2916 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_72590301 |
| source | MEDLINE; Springer Nature - Complete Springer Journals; Nature Journals Online |
| subjects | Adoptive Transfer Animals Apoptosis - drug effects Bacteremia - drug therapy Bacteremia - microbiology Bacteremia - pathology Biomedical and Life Sciences Biomedicine Caspase 3 Caspase Inhibitors Caspases - genetics Colony Count, Microbial Cysteine Proteinase Inhibitors - pharmacology Female Homeodomain Proteins - genetics Homeodomain Proteins - metabolism Humans Immunology In Vitro Techniques Infectious Diseases Inhibitors Interferon-gamma - biosynthesis Interleukin-2 - biosynthesis Lymphocytes Lymphocytes - drug effects Lymphocytes - pathology Mice Mice, Knockout Prevention Sepsis - drug therapy Sepsis - pathology Survival |
| title | Caspase inhibitors improve survival in sepsis: a critical role of the lymphocyte |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-01T21%3A56%3A04IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Caspase%20inhibitors%20improve%20survival%20in%20sepsis:%20a%20critical%20role%20of%20the%20lymphocyte&rft.jtitle=Nature%20immunology&rft.au=Hotchkiss,%20R.%20S.&rft.date=2000-12-01&rft.volume=1&rft.issue=6&rft.spage=496&rft.epage=501&rft.pages=496-501&rft.issn=1529-2908&rft.eissn=1529-2916&rft_id=info:doi/10.1038/82741&rft_dat=%3Cgale_proqu%3EA188805796%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=222713069&rft_id=info:pmid/11101871&rft_galeid=A188805796&rfr_iscdi=true |